Hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or health-care-associated pneumonia (HCAP) suspected or confirmed to be due to Gram-positive pathogens. MedDRA version: 9.1 Level: LLT Classification code 10035664 Term: Pneumonia
Conditions
Interventions
Product Name: Iclaprim
Product Code: AR-100
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: iclaprim
CAS Number: 192314-93-5
Current Sponsor code: AR-100
Concentration
Sponsors
Arpida AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be considered for further screening procedures in this study only if they meet both of the following criteria: 1. Suspected or confirmed acute bacterial pneumonia due to Gram-positive pathogens in one of the following subgroups: - hospital-acquired pneumonia (HAP), i.e., pneumonia that occurs 48 hours or more after admission, which was not incubating at the time of admission; or - ventilator-associated pneumonia (VAP), i.e., pneumonia that arises more than 48 hours after endotracheal intubation; or - healthcare-associated pneumonia (HCAP), i.e., pneumonia diagnosed within 48 hours of hospital admission, in a patient who fulfills at least one of the following criteria: - hospitalization for at least two days within 90 days of the current infection, - residence in a nursing home or long-term care facility, - recipient of intravenous antibiotic therapy, chemotherapy, or wound care within 30 days of the current infection 2. Venous access available for intravenous dosing. 3. At least 2 of the following signs and symptoms typical of acute bacterial pneumonia: - cough, - new onset of purulent sputum production or a change (worsening) in character of the sputum, - auscultatory findings on pulmonary examination of rales and/or pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony), - dyspnea, tachypnea, or hypoxemia with a partial pressure oxygen (PO2) 38oC/100.4oF, tympanic temperature >38.5oC/101.2oF, rectal/core temperature >39.0oC/102.2oF) or hypothermia (rectal/core temperature 30 breaths per minute, - pulse rate =120 beats per minute (bpm), - altered mental status, - leucocytosis with white blood cell (WBC) count >10,000/mm3, - leucopenia with WBC count 15% immature neutrophils (bands), regardless of total peripheral WBC count. 4. Pulmonary infiltration consistent with the diagnosis of pneumonia (new or progressive infiltrates, consolidation, or pleural effusion) documented by chest X ray within 48 hours prior to randomization, as interpreted by the radiologist or investigator. The infiltrate must be new, and not likely to be related to another clinical process or condition (for example, congestive heart failure or acute respiratory distress syndrome), as judged by the investigator. 5. Suitable respiratory specimen (sputum/endotracheal specimen or specimen from invasive procedure) for culture, and Gram stain, with indication of Gram-positive pathogens. Average of at least 10 organisms per oil-immersion field in 10 fields (actual or calculated, 100x objective). For sputum samples, additionally fulfilling both of the following criteria: - =10 squamous epithelial cells, and - =25 leucocytes per low power field (100x) in 10 to 20 fields. If the above two criteria are not met, a justification should be entered into the CRF. If the baseline respiratory specimen is obtained by an invasive technique (bronchoscopic or non-bronchoscopic), it is acceptable to obtain the specimen within 24 hours after starting study drug. 6. CPIS >6 7. For females only: - post-menopausal for at least 1 year, or - history of hysterectomy or tubal ligation, or - nega
Exclusion criteria
Exclusion criteria: 1. APACHE II score 40 kg/m2. 18. Body weight 133 kg. 19. Any underlying condition or disease that would interfere with the completion of the study procedures or any other condition that in the opinion of the investigator, would confound or interfere with the evaluation of safety or efficacy of the investigational medication, or prevent compliance with the study protocol. 20. Known or suspected hypersensitivity to trimethoprim, iclaprim, or vancomycin, or corresponding excipients. 21. Severe hepatic disease (Child-Pugh Class C), or bilirubin >1.5 x upper limit of normal (ULN) and/or alanine transaminase (ALT) >3 x ULN. 22. Any of the following cardiovascular conditions or risk factors: - known to have congenital or sporadic syndromes of QTc prolongation, - concomitant type IA (such as propafenone, flecainide) or III (such as amiodarone, sotalol) anti-arrhythmic drugs, - nonsustained ventricular tachycardia (NSVT) defined as =10 consecutive ventricular beats at a rate of >120 bpm with a duration of 470
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the clinical cure rates of the 0.8 mg/kg q12h and 1.2 mg/kg q8h dosing regimens of iclaprim with vancomycin (q12h) in the treatment of patients with hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or health-care associated pneumonia (HCAP) suspected or confirmed to be due to Gram-positive pathogens.;Secondary Objective: To compare the 0.8 mg/kg q12h and 1.2 mg/kg q8h dosing regimens of iclaprim with vancomycin as well as to each other for the following parameters: - Proportion of patients who had died by Day 28, - Time to death (censored at Day 28, if alive), - Proportion of patients with clinical pulmonary infection score (CPIS) of 6 or less approximately 72 hours after start of infusion with study medication (i.e., by Day 4), - Microbiological outcome at End of Therapy (EOT) and Test of Cure (TOC), - Safety and tolerability, - Clinical cure rate (iclaprim q12h versus q8h). In addition, pharmacokinetic analysis including population pharmacokinetics, will be conducted. ;Primary end point(s): Efficacy: Clinical cure rate at TOC – comparison of the two iclaprim dosing regimens (0.8 mg/kg q12h and 1.2 mg/kg q8h) versus vancomycin (q12h). | — |
Countries
Estonia, Latvia, Lithuania
Outcome results
None listed